Is ABR p.Ser499Phe (c.1496C>T) pathogenic?

ABR p.Ser499Phe (c.1496C>T) is classified Uncertain significance in ABR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.1659); Ultra-rare (popmax 0.012%, afr).

How common is ABR p.Ser499Phe (c.1496C>T) in the general population?

ABR p.Ser499Phe (c.1496C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about ABR p.Ser499Phe (c.1496C>T)?

AlphaMissense predicts likely benign (score 0.1659) — an in-silico prediction, not a clinical call.

ABR p.Ser499Phe

c.1496C>T · rs773646538 · VCV3132374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1659 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1659	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -13.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 51 kb · p 4.1e-18 · regional, not allelic
Overall
CADD	31.0	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 0.012% African / African-American · 9/74,940 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00118% 19/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,327
Admixed American	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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: ABR
Protein: p.Ser499Phe
Coding: c.1496C>T
MANE Select: NM_021962
dbSNP: rs773646538
Type: single nucleotide variant
Location: chr17:1056100 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.10
Residue 499: the c2 domain

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

Similar variants

ABR c.2490+4C>T Benign ★★ same type
ABR p.Ala31Glu Benign ★★ same type
ABR p.Arg124Gln Benign ★★ same type
ABR p.Glu73Asp Benign ★★ same type
ABR p.Gly114Glu Benign ★★ same type
ABR p.Gly66= Benign ★★ same type
ABR p.Ala62Thr Uncertain significance ★ ⚠ same type
ABR p.Ala688Thr 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/abr-p-ser499phe (accessed [today's date]).

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