Is ABHD12 p.Ser21Phe (c.62C>T) pathogenic?

ABHD12 p.Ser21Phe (c.62C>T) is classified Uncertain significance in ABHD12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1022); Ultra-rare (popmax 0.0462%, mid); Associated with inherited retinal dystrophy.

What condition is associated with ABHD12 p.Ser21Phe (c.62C>T)?

ABHD12 p.Ser21Phe (c.62C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ABHD12 p.Ser21Phe (c.62C>T) in the general population?

ABHD12 p.Ser21Phe (c.62C>T) is ultra-rare (popmax 0.0462%, mid) (gnomAD).

What do computational predictors say about ABHD12 p.Ser21Phe (c.62C>T)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

ABHD12 p.Ser21Phe

c.62C>T · rs773035473 · VCV1497185

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -10.32	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
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	25.4	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 0.0462% Middle Eastern · 2/4,328 alleles

Filtering AF 0.0328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.00338% 49/1,449,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0462%	2,164
South Asian	0.0447%	2,239
Remaining individualsnot grpmax-eligible	0.00723%	13,840
African / African-American	0.00297%	33,714
Admixed American	0.00255%	39,178
European (non-Finnish)	0.000543%	184,225

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: ABHD12
Protein: p.Ser21Phe
Coding: c.62C>T
MANE Select: NM_001042472
dbSNP: rs773035473
Type: single nucleotide variant
Location: chr20:25390642 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60

Full ABHD12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABHD12 p.Ser21= Likely benign ★ same residue
ABHD12 p.Arg65Ter Pathogenic ★ same condition
ABHD12 p.Arg257Trp Conflicting classifications of pathogenicity ★ same condition
ABHD12 p.Val68Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
ABHD12 c.620-2A>G Likely pathogenic same condition
ABHD12 p.Gly209Arg Uncertain significance ⚠ same condition
ABHD12 c.1029+1G>T Likely pathogenic ★★ same type
ABHD12 p.Arg262Ter Pathogenic ★★ 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/abhd12-p-ser21phe (accessed [today's date]).

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