Is FLNA p.Ser2010Pro (c.6028T>C) pathogenic?

FLNA p.Ser2010Pro (c.6028T>C) is classified Benign in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-27). AlphaMissense: likely pathogenic (0.9962); Very rare (popmax 0.00873%, afr); Associated with heterotopia, periventricular, X-linked dominant.

What condition is associated with FLNA p.Ser2010Pro (c.6028T>C)?

FLNA p.Ser2010Pro (c.6028T>C) is associated with heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Ser2010Pro (c.6028T>C) in the general population?

FLNA p.Ser2010Pro (c.6028T>C) is very rare (popmax 0.00873%, afr) (gnomAD).

What do computational predictors say about FLNA p.Ser2010Pro (c.6028T>C)?

AlphaMissense predicts likely pathogenic (score 0.9962) — an in-silico prediction, not a clinical call.

FLNA p.Ser2010Pro

c.6028T>C · VCV4783032

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00873%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotopia, periventricular, X-linked dominant

Computational evidence

Protein change
AlphaMissense	0.9962	likely pathogenic · top 5% in FLNA
REVEL	0.661	pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.85, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	24.4	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 0.00873% African / African-American · 5/57,267 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.000413% 5/1,210,015 alleles · very rare exomes 1/1,097,709 · genomes 4/112,306 · joint denominator

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.Ser2010Pro
Coding: c.6028T>C
MANE Select: NM_001110556
Type: single nucleotide variant
Location: chrX:154353199 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2010: a β-strand

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

Disease context

heterotopia, periventricular, X-linked dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia

Similar variants

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
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-ser2010pro (accessed [today's date]).

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