Is EGFLAM p.Ala922= (c.2766C>T) pathogenic?

EGFLAM p.Ala922= (c.2766C>T) is classified Likely benign in EGFLAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Ultra-rare (popmax 0.033%, mid).

How common is EGFLAM p.Ala922= (c.2766C>T) in the general population?

EGFLAM p.Ala922= (c.2766C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

EGFLAM p.Ala922=

c.2766C>T · rs371848483 · VCV2655435

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -4.9	GERP -3.1
Overall
CADD	4.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,056 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00626% 101/1,613,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
Middle Easterngrpmax	0.033%	3,028
Finnishnot grpmax-eligible	0.0156%	6,402
Admixed American	0.0117%	8,567
Remaining individualsnot grpmax-eligible	0.0096%	10,415
African / African-American	0.00933%	10,716
European (non-Finnish)	0.00381%	26,220
South Asian	0.0011%	91,064

Ashkenazi Jewish 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.Ala922=
Coding: c.2766C>T
MANE Select: NM_152403
dbSNP: rs371848483
Type: single nucleotide variant
Location: chr5:38458389 (GRCh38)
Gene constraint: LOEUF 0.83 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.81 · 3 PDB
Residue 922: a β-strand; the laminin g-like 3 domain

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-ala922 (accessed [today's date]).

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