Is FLNA p.Asp625= (c.1875C>T) pathogenic?

FLNA p.Asp625= (c.1875C>T) is classified Conflicting classifications of pathogenicity in FLNA (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-02-03). Rare (popmax 0.242%, nfe); Associated with connective tissue disorder.

What condition is associated with FLNA p.Asp625= (c.1875C>T)?

FLNA p.Asp625= (c.1875C>T) is associated with connective tissue disorder, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Asp625= (c.1875C>T) in the general population?

FLNA p.Asp625= (c.1875C>T) is rare (popmax 0.242%, nfe) (gnomAD).

FLNA p.Asp625=

c.1875C>T · rs200660642 · VCV194196

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.242%, nfe)

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.76, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.242% European (non-Finnish) · 2,165/894,823 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.23%

Overall 0.189% 2,280/1,208,470 alleles · rare exomes 2,127/1,097,681 · genomes 153/110,789 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.242%	413
Remaining individualsnot grpmax-eligible	0.181%	553
African / African-American	0.0229%	4,374
Admixed American	0.0197%	5,082
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,338
Finnishnot grpmax-eligible	0.00435%	23,004
South Asian	0.00353%	28,342

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.Asp625=
Coding: c.1875C>T
MANE Select: NM_001110556
dbSNP: rs200660642
Type: single nucleotide variant
Location: chrX:154364673 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 625: a β-strand

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection

Similar variants

FLNA p.Asp625Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.2022+1G>A Pathogenic ★★ same condition
FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same condition
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

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-asp625 (accessed [today's date]).

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