Is CD44 p.Arg673Gln (c.2018G>A) pathogenic?

CD44 p.Arg673Gln (c.2018G>A) is classified Likely benign in CD44 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-27). AlphaMissense: likely pathogenic (0.607); Rare (popmax 0.289%, nfe).

How common is CD44 p.Arg673Gln (c.2018G>A) in the general population?

CD44 p.Arg673Gln (c.2018G>A) is rare (popmax 0.289%, nfe) (gnomAD).

What do computational predictors say about CD44 p.Arg673Gln (c.2018G>A)?

AlphaMissense predicts likely pathogenic (score 0.607) — an in-silico prediction, not a clinical call.

CD44 p.Arg673Gln

c.2018G>A · rs61752932 · VCV717300

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.607 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.289%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.607	likely pathogenic
REVEL	0.24	benign-leaning
SaProt	LLR -10.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.099 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.289% European (non-Finnish) · 3,413/1,179,762 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.278%

Overall 0.263% 4,252/1,613,846 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.944%	106
European (non-Finnish)grpmax	0.289%	346
Remaining individualsnot grpmax-eligible	0.235%	425
East Asian	0.0423%	2,362
African / African-American	0.0333%	3,001
South Asian	0.0318%	3,141
Admixed American	0.0217%	4,617
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,799

Finnish 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: CD44
Protein: p.Arg673Gln
Coding: c.2018G>A
MANE Select: NM_000610
dbSNP: rs61752932
Type: single nucleotide variant
Location: chr11:35221726 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 673: the 'required for interaction with ezr, msn and rdx and for co-localization to microvilli' region

Full CD44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD44 c.367+7T>C Benign ★★ same type
CD44 p.Arg463Gln Benign ★★ same type
CD44 p.Gly462= Benign ★★ same type
CD44 p.Ile457Val Benign ★★ same type
CD44 p.Phe245= Benign ★★ same type
CD44 p.Thr163= Benign ★★ same type
CD44 p.Thr393Met Benign ★★ ⚠ same type
CD44 p.Thr415= Benign ★★ 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/cd44-p-arg673gln (accessed [today's date]).

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