Is CD74 p.Gly63Ser (c.187G>A) pathogenic?

CD74 p.Gly63Ser (c.187G>A) is classified Uncertain significance in CD74 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.3041); Absent from gnomAD v4.1.

How common is CD74 p.Gly63Ser (c.187G>A) in the general population?

CD74 p.Gly63Ser (c.187G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD74 p.Gly63Ser (c.187G>A)?

AlphaMissense predicts likely benign (score 0.3041) — an in-silico prediction, not a clinical call.

CD74 p.Gly63Ser

c.187G>A · rs2534792949 · VCV2559951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3041 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3041	likely benign
REVEL	0.564	indeterminate
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 0.67, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.009 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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: CD74
Protein: p.Gly63Ser
Coding: c.187G>A
MANE Select: NM_001025159
dbSNP: rs2534792949
Type: single nucleotide variant
Location: chr5:150407263 (GRCh38)
Gene constraint: LOEUF 0.849 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.49 · 24 PDB
Residue 63: an α-helix

Full CD74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD74 p.Ala117Thr Uncertain significance ★ ⚠ same type
CD74 p.Arg108Gly Uncertain significance ★ ⚠ same type
CD74 p.Arg108His Uncertain significance ★ ⚠ same type
CD74 p.Arg167Ser Uncertain significance ★ ⚠ same type
CD74 p.Arg35Gly Uncertain significance ★ ⚠ same type
CD74 p.Arg46His Uncertain significance ★ ⚠ same type
CD74 p.Arg77Trp Uncertain significance ★ ⚠ same type
CD74 p.Arg94His 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/cd74-p-gly63ser (accessed [today's date]).

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