Is FLNA p.Pro2423Ser (c.7267C>T) pathogenic?

FLNA p.Pro2423Ser (c.7267C>T) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-30). AlphaMissense: likely benign (0.1514); Ultra-rare (popmax 0.0756%, nfe); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Pro2423Ser (c.7267C>T)?

FLNA p.Pro2423Ser (c.7267C>T) is associated with Melnick-Needles syndrome, connective tissue disorder, intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked (ClinVar).

How common is FLNA p.Pro2423Ser (c.7267C>T) in the general population?

FLNA p.Pro2423Ser (c.7267C>T) is ultra-rare (popmax 0.0756%, nfe) (gnomAD).

What do computational predictors say about FLNA p.Pro2423Ser (c.7267C>T)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

FLNA p.Pro2423Ser

c.7267C>T · rs200198847 · VCV213485

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0756%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Melnick-Needles syndrome

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0756% European (non-Finnish) · 677/894,942 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.069%

Overall 0.0616% 745/1,210,258 alleles · ultra-rare exomes 696/1,097,626 · genomes 49/112,632 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0756%	1,322
Remaining individualsnot grpmax-eligible	0.0652%	1,535
Finnishnot grpmax-eligible	0.0472%	2,117
Middle Eastern	0.0229%	4,374
Ashkenazi Jewishnot grpmax-eligible	0.0227%	4,407
South Asian	0.00703%	14,229
African / African-American	0.00697%	14,344
Admixed American	0.00217%	45,984

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FLNA
Protein: p.Pro2423Ser
Coding: c.7267C>T
MANE Select: NM_001110556
dbSNP: rs200198847
Type: single nucleotide variant
Location: chrX:154350097 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

Full FLNA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Melnick-Needles syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: connective tissue disorder intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked heterotopia, periventricular, X-linked dominant terminal osseous dysplasia-pigmentary defects syndrome FG syndrome 2 otopalatodigital syndrome type 2 otopalatodigital syndrome type 1 cardiac valvular dysplasia, X-linked frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection frontometaphyseal dysplasia 1

Similar variants

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FLNA c.5417-2A>G Likely pathogenic ★★ same condition
FLNA c.868+1G>A Likely pathogenic ★★ same condition
FLNA c.987+1G>A Likely pathogenic ★★ same condition
FLNA p.Ala1188Thr Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Arg1515Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/flna-p-pro2423ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown