Is EGFLAM p.Val131= (c.393C>G) pathogenic?

EGFLAM p.Val131= (c.393C>G) is classified Likely benign in EGFLAM (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-01). Rare (popmax 0.194%, sas).

How common is EGFLAM p.Val131= (c.393C>G) in the general population?

EGFLAM p.Val131= (c.393C>G) is rare (popmax 0.194%, sas) (gnomAD).

EGFLAM p.Val131=

c.393C>G · rs148290116 · VCV2655434

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.194%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -2.4, phastCons 1
Overall
CADD	3.665	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.194% South Asian · 177/91,018 alleles

Filtering AF 0.172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.169%

Overall 0.168% 2,709/1,613,998 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.04%	20
Finnishnot grpmax-eligible	0.326%	306
South Asiangrpmax	0.194%	514
European (non-Finnish)	0.178%	561
Ashkenazi Jewishnot grpmax-eligible	0.149%	673
Remaining individualsnot grpmax-eligible	0.12%	833
Admixed American	0.045%	2,223
Middle Eastern	0.033%	3,031
African / African-American	0.032%	3,127
East Asian	0.00223%	44,874

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EGFLAM
Protein: p.Val131=
Coding: c.393C>G
MANE Select: NM_152403
dbSNP: rs148290116
Type: single nucleotide variant
Location: chr5:38350602 (GRCh38)
Gene constraint: LOEUF 0.83 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.81 · 3 PDB
Residue 131: the fibronectin type-iii 1 domain; a β-strand

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

Similar variants

EGFLAM p.Asn913= Benign ★★ same type
EGFLAM p.Trp229Arg Benign ★★ same type
EGFLAM c.2465-2611T>C Uncertain significance ★ ⚠ same type
EGFLAM p.Ala115Val Uncertain significance ★ ⚠ same type
EGFLAM p.Ala143Pro Uncertain significance ★ ⚠ same type
EGFLAM p.Ala314Thr Uncertain significance ★ ⚠ same type
EGFLAM p.Ala45Thr Uncertain significance ★ ⚠ same type
EGFLAM p.Ala515Thr Uncertain significance ★ ⚠ 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/egflam-p-val131 (accessed [today's date]).

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