Is CD164 p.Ser74Arg (c.222C>A) pathogenic?

CD164 p.Ser74Arg (c.222C>A) is classified Uncertain significance in CD164 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.5329); Very rare (popmax 0.00668%, afr).

How common is CD164 p.Ser74Arg (c.222C>A) in the general population?

CD164 p.Ser74Arg (c.222C>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CD164 p.Ser74Arg (c.222C>A)?

AlphaMissense predicts ambiguous (score 0.5329) — an in-silico prediction, not a clinical call.

CD164 p.Ser74Arg

c.222C>A · VCV3829389

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5329	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -12.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -2.8, phastCons 0.001
Regional constraint	o/e 1.21	unconstrained · MANE · 14 kb · p 0.001 · regional, not allelic
Overall
CADD	15.35	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 0.00668% African / African-American · 5/74,894 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000496% 8/1,613,384 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,979
Admixed American	0.00334%	29,953
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: CD164
Protein: p.Ser74Arg
Coding: c.222C>A
MANE Select: NM_006016
Type: single nucleotide variant
Location: chr6:109379616 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 67.15

Full CD164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD164 p.Ser74Asn Benign/Likely benign ★★ ⚠ same residue
CD164 p.Arg192Ter Uncertain significance ★★ same type
CD164 p.Asn121Ser Uncertain significance ★★ ⚠ same type
CD164 p.Asn32Lys Uncertain significance ★★ ⚠ same type
CD164 p.Asp107Asn Uncertain significance ★★ ⚠ same type
CD164 p.Leu15Val Uncertain significance ★★ ⚠ same type
CD164 p.Leu183Pro Uncertain significance ★★ ⚠ same type
CD164 p.Leu9Phe 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/cd164-p-ser74arg (accessed [today's date]).

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