Is CHAD p.Ser208Phe (c.623C>T) pathogenic?

CHAD p.Ser208Phe (c.623C>T) is classified Uncertain significance in CHAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.2158); Very rare (popmax 0.00223%, eas).

How common is CHAD p.Ser208Phe (c.623C>T) in the general population?

CHAD p.Ser208Phe (c.623C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CHAD p.Ser208Phe (c.623C>T)?

AlphaMissense predicts likely benign (score 0.2158) — an in-silico prediction, not a clinical call.

CHAD p.Ser208Phe

c.623C>T · rs1391168025 · VCV2525076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2158	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.6	GERP -1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,512 bp · p 0.21 · regional, not allelic
Overall
CADD	27.0	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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,074 alleles · very rare exomes 1/1,461,708 · genomes 2/152,366 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
European (non-Finnish)	0.00017%	589,971

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: CHAD
Protein: p.Ser208Phe
Coding: c.623C>T
MANE Select: NM_001267
dbSNP: rs1391168025
Type: single nucleotide variant
Location: chr17:50468191 (GRCh38)

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

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/chad-p-ser208phe (accessed [today's date]).

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