Is FLNC p.Pro1938= (c.5814G>A) pathogenic?

FLNC p.Pro1938= (c.5814G>A) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-27). Very rare (popmax 0.00768%, sas); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Pro1938= (c.5814G>A)?

FLNC p.Pro1938= (c.5814G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Pro1938= (c.5814G>A) in the general population?

FLNC p.Pro1938= (c.5814G>A) is very rare (popmax 0.00768%, sas) (gnomAD).

FLNC p.Pro1938=

c.5814G>A · rs752263141 · VCV774448

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

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 -15
Overall
CADD	0.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00768% South Asian · 7/91,092 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00285% 46/1,613,766 alleles · very rare exomes 44/1,461,596 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	0.00288%	34,707
African / African-American	0.00267%	37,460
Admixed American	0.00167%	60,000

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.Pro1938=
Coding: c.5814G>A
MANE Select: NM_001458
dbSNP: rs752263141
Type: single nucleotide variant
Location: chr7:128851600 (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: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

Similar variants

FLNC p.Pro1938Leu Uncertain significance ★★ ⚠ same residue
FLNC p.Pro1938Arg 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-pro1938 (accessed [today's date]).

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