Is EGF p.Ser155Arg (c.465T>G) pathogenic?

EGF p.Ser155Arg (c.465T>G) is classified Uncertain significance in EGF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-14). AlphaMissense: likely benign (0.1439); Ultra-rare (popmax 0.0213%, afr).

How common is EGF p.Ser155Arg (c.465T>G) in the general population?

EGF p.Ser155Arg (c.465T>G) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about EGF p.Ser155Arg (c.465T>G)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

EGF p.Ser155Arg

c.465T>G · rs138035348 · VCV1941820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -4.1
Regional constraint	o/e 0.90	unconstrained · MANE · 68 kb · p 0.00042 · regional, not allelic
Overall
CADD	1.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0213% African / African-American · 16/74,942 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00112% 18/1,613,696 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,684
Admixed American	0.00167%	60,006
European (non-Finnish)	8.48e-05%	1,179,798

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: EGF
Protein: p.Ser155Arg
Coding: c.465T>G
MANE Select: NM_001963
dbSNP: rs138035348
Type: single nucleotide variant
Location: chr4:109943391 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.66 · 13 PDB

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

Similar variants

EGF p.Ser155Asn Uncertain significance ★★ ⚠ same residue
EGF c.2221+4C>T Uncertain significance ★★ same type
EGF c.2858-11G>T Uncertain significance ★★ same type
EGF c.-60C>T Uncertain significance ★★ same type
EGF p.Ala1025Ser Uncertain significance ★★ ⚠ same type
EGF p.Ala1037Val Uncertain significance ★★ ⚠ same type
EGF p.Ala45Val Uncertain significance ★★ ⚠ same type
EGF p.Ala862Thr 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/egf-p-ser155arg (accessed [today's date]).

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