Is FLNA p.Pro211Arg (c.632C>G) pathogenic?

FLNA p.Pro211Arg (c.632C>G) is classified Likely pathogenic in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-20). AlphaMissense: likely pathogenic (0.9195); Absent from gnomAD v4.1.

How common is FLNA p.Pro211Arg (c.632C>G) in the general population?

FLNA p.Pro211Arg (c.632C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Pro211Arg (c.632C>G)?

AlphaMissense predicts likely pathogenic (score 0.9195) — an in-silico prediction, not a clinical call.

FLNA p.Pro211Arg

c.632C>G · rs1057518109 · VCV372971

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9195 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9195	likely pathogenic ✓ concordant with ClinVar
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 4,344 bp · p 1.3e-27 · regional, not allelic
Overall
CADD	24.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNA
Protein: p.Pro211Arg
Coding: c.632C>G
MANE Select: NM_001110556
dbSNP: rs1057518109
Type: single nucleotide variant
Location: chrX:154367729 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 211: the 'actin-binding' region; the calponin-homology (ch) 2 domain

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

Similar variants

FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same type
FLNA c.2022+1G>A Pathogenic ★★ same type
FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same type
FLNA c.4599-1G>A Pathogenic/Likely pathogenic ★★ same type
FLNA c.5417-2A>G Likely pathogenic ★★ same type
FLNA c.5861-2A>G Pathogenic/Likely pathogenic ★★ same type
FLNA c.868+1G>A Likely pathogenic ★★ same type
FLNA c.987+1G>A Likely pathogenic ★★ same type

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-pro211arg (accessed [today's date]).

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