Is FLNC p.Glu634= (c.1902G>A) pathogenic?

FLNC p.Glu634= (c.1902G>A) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.72%, mid); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Glu634= (c.1902G>A)?

FLNC p.Glu634= (c.1902G>A) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 5 (ClinVar).

How common is FLNC p.Glu634= (c.1902G>A) in the general population?

FLNC p.Glu634= (c.1902G>A) is low-frequency (popmax 1.72%, mid) (gnomAD).

FLNC p.Glu634=

c.1902G>A · rs12536635 · VCV194038

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.72%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.6	phastCons 1
Overall
CADD	9.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.72% Middle Eastern · 104/6,060 alleles

Filtering AF 1.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.35%

Overall 0.611% 9,858/1,614,090 alleles · low-frequency exomes 9,245/1,461,814 · genomes 613/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.72%	58
Ashkenazi Jewishnot grpmax-eligible	0.767%	130
European (non-Finnish)	0.742%	135
Remaining individualsnot grpmax-eligible	0.526%	190
Admixed American	0.403%	248
African / African-American	0.123%	816
Finnishnot grpmax-eligible	0.0984%	1,016
South Asian	0.0516%	1,938
East Asian	0.00223%	44,878

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: FLNC
Protein: p.Glu634=
Coding: c.1902G>A
MANE Select: NM_001458
dbSNP: rs12536635
Type: single nucleotide variant
Location: chr7:128841258 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

Similar variants

FLNC p.Glu634Asp Uncertain significance ★ ⚠ same residue
FLNC p.Glu634Gln Uncertain significance ★ 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
FLNC c.2550+1G>C 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-glu634 (accessed [today's date]).

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