Is FLNC p.Val312Ile (c.934G>A) pathogenic?

FLNC p.Val312Ile (c.934G>A) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-24). AlphaMissense: likely benign (0.2069); Absent from gnomAD v4.1; Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Val312Ile (c.934G>A)?

FLNC p.Val312Ile (c.934G>A) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Val312Ile (c.934G>A) in the general population?

FLNC p.Val312Ile (c.934G>A) is absent from gnomAD v4.1 (gnomAD).

How is Muscle filaminopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FLNC p.Val312Ile (c.934G>A)?

AlphaMissense predicts likely benign (score 0.2069) — an in-silico prediction, not a clinical call.

FLNC p.Val312Ile

c.934G>A · rs2128934250 · VCV1432056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2069 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 5

Computational evidence

Protein change
AlphaMissense	0.2069	likely benign
REVEL	0.653	pathogenic-leaning
SaProt	LLR -11.97	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 11 kb · p 8.4e-13 · regional, not allelic
Overall
CADD	25.4	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

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: FLNC
Protein: p.Val312Ile
Coding: c.934G>A
MANE Select: NM_001458
dbSNP: rs2128934250
Type: single nucleotide variant
Location: chr7:128837720 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

myofibrillar myopathy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

For Muscle filaminopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FLNC p.Val312Gly Uncertain significance ★ ⚠ same residue
FLNC p.Val312= Likely benign ★ same residue
FLNC p.Val312fs Likely pathogenic ★ same residue
FLNC c.1047+1G>T Likely pathogenic ★★ same condition
FLNC c.1048-1G>A Likely pathogenic ★★ same condition
FLNC c.1210+1G>A Likely pathogenic ★★ same condition
FLNC c.1549+2T>G Likely pathogenic ★★ same condition
FLNC c.2007+1G>A 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/flnc-p-val312ile (accessed [today's date]).

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