Is EGFLAM p.Phe675Ser (c.2024T>C) pathogenic?

EGFLAM p.Phe675Ser (c.2024T>C) is classified Uncertain significance in EGFLAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: likely pathogenic (0.9786); Absent from gnomAD v4.1.

How common is EGFLAM p.Phe675Ser (c.2024T>C) in the general population?

EGFLAM p.Phe675Ser (c.2024T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGFLAM p.Phe675Ser (c.2024T>C)?

AlphaMissense predicts likely pathogenic (score 0.9786) — an in-silico prediction, not a clinical call.

EGFLAM p.Phe675Ser

c.2024T>C · rs2530813590 · VCV2332763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9786 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9786	likely pathogenic · top 1% in EGFLAM
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -13.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 205 kb · p 0.46 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: EGFLAM
Protein: p.Phe675Ser
Coding: c.2024T>C
MANE Select: NM_152403
dbSNP: rs2530813590
Type: single nucleotide variant
Location: chr5:38427222 (GRCh38)
Gene constraint: LOEUF 0.83 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.81 · 3 PDB
Residue 675: the laminin g-like 2 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-phe675ser (accessed [today's date]).

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