Is ALG12 p.Phe317Leu (c.951C>A) pathogenic?

ALG12 p.Phe317Leu (c.951C>A) is classified Uncertain significance in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely pathogenic (0.7555); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Phe317Leu (c.951C>A)?

ALG12 p.Phe317Leu (c.951C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALG12 p.Phe317Leu (c.951C>A) in the general population?

ALG12 p.Phe317Leu (c.951C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG12 p.Phe317Leu (c.951C>A)?

AlphaMissense predicts likely pathogenic (score 0.7555) — an in-silico prediction, not a clinical call.

ALG12 p.Phe317Leu

c.951C>A · rs1480401201 · VCV2537868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7555 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7555	likely pathogenic
REVEL	0.134	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.35, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	19.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG12
Protein: p.Phe317Leu
Coding: c.951C>A
MANE Select: NM_024105
dbSNP: rs1480401201
Type: single nucleotide variant
Location: chr22:49907762 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26

Full ALG12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG12 p.Phe317= Likely benign ★ same residue
ALG12 p.Ala135Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala290Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala300Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala357Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala411Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Arg10Trp Uncertain significance ★★ ⚠ same condition
ALG12 p.Arg120Trp Uncertain significance ★★ ⚠ same condition

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/alg12-p-phe317leu (accessed [today's date]).

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