Is CA5A p.Val172Leu (c.514G>T) pathogenic?

CA5A p.Val172Leu (c.514G>T) is classified Conflicting classifications of pathogenicity in CA5A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-03-02). AlphaMissense: likely benign (0.0785); Ultra-rare (popmax 0.0165%, sas); Associated with Inborn genetic diseases.

What condition is associated with CA5A p.Val172Leu (c.514G>T)?

CA5A p.Val172Leu (c.514G>T) is associated with Inborn genetic diseases, hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (ClinVar).

How common is CA5A p.Val172Leu (c.514G>T) in the general population?

CA5A p.Val172Leu (c.514G>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about CA5A p.Val172Leu (c.514G>T)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

CA5A p.Val172Leu

c.514G>T · rs142182110 · VCV1495000

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.027 · regional, not allelic
Overall
CADD	0.002	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 0.0165% South Asian · 15/91,050 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00186% 30/1,612,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,070
Finnishnot grpmax-eligible	0.00625%	16,009
African / African-American	0.00267%	37,449
Remaining individualsnot grpmax-eligible	0.0016%	62,436
European (non-Finnish)	0.000679%	147,325

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: CA5A
Protein: p.Val172Leu
Coding: c.514G>T
MANE Select: NM_001739
dbSNP: rs142182110
Type: single nucleotide variant
Location: chr16:87902466 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 172: the alpha-carbonic anhydrase domain

Full CA5A 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

Also linked: hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency

Similar variants

CA5A p.Val172Met Uncertain significance ★ ⚠ same residue
CA5A p.Arg32Ter Pathogenic ★★ same condition
CA5A p.Glu241Lys Pathogenic/Likely pathogenic ★★ same condition
CA5A p.Ala149Thr Uncertain significance ★★ ⚠ same condition
CA5A p.Ala208Val Uncertain significance ★★ ⚠ same condition
CA5A p.Ala261Val Uncertain significance ★★ ⚠ same condition
CA5A p.Arg26His Uncertain significance ★★ ⚠ same condition
CA5A p.Asp216Ala 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/ca5a-p-val172leu (accessed [today's date]).

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