Is SUCLA2 p.Val71Phe (c.211G>T) pathogenic?

SUCLA2 p.Val71Phe (c.211G>T) is classified Uncertain significance in SUCLA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.6626); Very rare (popmax 0.00517%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SUCLA2 p.Val71Phe (c.211G>T)?

SUCLA2 p.Val71Phe (c.211G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SUCLA2 p.Val71Phe (c.211G>T) in the general population?

SUCLA2 p.Val71Phe (c.211G>T) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about SUCLA2 p.Val71Phe (c.211G>T)?

AlphaMissense predicts likely pathogenic (score 0.6626) — an in-silico prediction, not a clinical call.

SUCLA2 p.Val71Phe

c.211G>T · VCV4177479

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6626	likely pathogenic
REVEL	0.505	indeterminate
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.3
Regional constraint	o/e 1.13	unconstrained · MANE · 12 kb · p 0.16 · regional, not allelic
Overall
CADD	11.25	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 0.00517% European (non-Finnish) · 61/1,179,944 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00403% 65/1,613,854 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,618
European (non-Finnish)grpmax	0.00517%	19,343

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SUCLA2
Protein: p.Val71Phe
Coding: c.211G>T
MANE Select: NM_003850
Type: single nucleotide variant
Location: chr13:47996903 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.45 · 2 PDB
Residue 71: the atp-grasp domain

Full SUCLA2 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

SUCLA2 p.Val71Ile Uncertain significance ★ ⚠ same residue
SUCLA2 p.Ala27Val Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Ala330Pro Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Asn276Ser Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Asp315Asn Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Cys158Tyr Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Glu206Gly Uncertain significance ★★ same condition
SUCLA2 p.Glu359Ala 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/sucla2-p-val71phe (accessed [today's date]).

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